Multi-disciplinary studies on diffuse degenerative diseases of the human brain, in particular those affecting children, have lead to the delineation of the neuronal ceroid-lipofuscinoses, a group of diseaes characterized by the accumulation of intracellular autofluorescent lipopigments, particularly severe in cerebral neurons. This pigment formation is due to an increased rate of peroxidation of polyunsaturated fatty acids and damages the affected cells, producing neuronal dysfunction and loss. Several clinically and presumably, genetically different conditions make up the neuronal ceroid-lipofuscinoses. However, the various diseases are quite similar with respect to the pathology and very similar to a disease in inbred English Setters inherited as an autosomal recessive. Practically all patients with neuronal ceroidlipofuscinosis as well as all affected dogs reveal a profound deficiency of a PPD-linked peroxidase, the activity of which averages 10% of normal controls. Whether the enzyme deficiency represents the genetically controlled underlying chemical defect will be investigated by determining the acivity of the enzyme in homologous parts of the brain obtained from affecteds and from age-matched controls selected for differential pathomorphological involvement. The isozyme pattern of the enzyme will be studied by starch gel electrophoresis and attempts at partial purification will be made. Therapeutic trials with lymphoblast tranplants, exogenous peroxidase, antioxidants and with inducers of peroxidase activity will be monitored by ethane evolution and improved in the light of the results obtained from the proposed studies.